The Spectrum of Gallbladder Disease

The Spectrum of

Gallbladder Disease

Rebecca Kowalski, M.D.

October 18, 2017

Overview

A (brief) history of gallbladder surgery

Anatomy

Anatomical variations

Physiology

Pathophysiology

Diagnostic imaging of the gallbladder

Natural history of cholelithiasis

Case presentations of the spectrum of gallstone disease

Summary

History of Gallbladder Surgery

Gallbladder Surgery: A Relatively Recent Change

Prior to the late 1800s, doctors treated gallbladder disease with a cholecystostomy, due to the fear that removing the organ would kill patients

Carl Johann August Langenbuch(director of the Lazarus Hospital in Berlin, Germany) practiced on a cadaver to remove the gallbladder, and in 1882, performed a cholecystectomy on a patient. He was discharged after 6 weeks in the hospital

By 1897 over 100 cholecystectomies had been performed

https://en.wikipedia.org/wiki/Carl_Langenbuch

Gallbladder Surgery: A Relatively Recent Change

In 1985, Erich Mühe removed a patient’s gallbladder laparoscopically in Germany

In 1987, Philippe Mouret (a French gynecologic surgeon) performed a laparoscopic cholecystectomy

In 1992, the National Institutes of Health (NIH) created guidelines for laparoscopic cholecystectomy in the United States, essentially transforming surgical practice

Erich Muhehttps://openi.nlm.ni

h.gov/detailedresult.

php?img=PMC30152

44_jsls-2-4-341-

g01&req=4

Philippe Mourethttps://www.pinterest.com

/pin/58195020154734720/

Anatomy and Abnormal Anatomy

http://accesssurgery.mhmedical.com/content.aspx?bookid=1202&sectionid=71521210

http://www.slideshare.net/pryce27/rsna-final-2



Physiology

http://www.nature.com/nrm/journal/v2/n9/fig_tab/nrm0901_657a_F3.html

a

Simplified overview of the bile acid biosynthesis pathway derived from cholesterol

Lisa D. Beilke et al. Drug Metab Dispos 2009;37:1035-1045

http://dmd.aspetjournals.org/content/37/5/1035

http://clinicalgate.com/liver-biliary-tract-and-pancreatic-disease/

http://clinicalgate.com/liver-biliary-tract-and-pancreatic-disease/

Gallbladder Function: Absorption and Secretion

Main function of the gallbladder is to concentrate and store

hepatic bile and to deliver bile into the duodenum in

response to a meal

In the fasting state, approximately 80% of the bile secreted

by the liver is stored in the gallbladder

Gallbladder Function: Absorption and Secretion(continued)

The gallbladder mucosa has the greatest absorptive power per

unit area of any structure in the body

Epithelial cells of the gallbladder secrete at least two

important products into the gallbladder lumen: glycoproteins

and hydrogen ions

https://www.barnardhealth.us/action

-potential/bile-secretion-and-gall-

bladder-function.html

https://courses.washington.edu/conj/bess/bile/bile.html

http://www.austincc.edu/apreview/PhysText/Digestive.html

Source: Gallbladder and the Extrahepatic Biliary System, Schwartz's Principles of Surgery, 10e

Citation: Brunicardi F, Andersen DK, Billiar TR, Dunn DL, Hunter JG, Matthews JB, Pollock RE. Schwartz's Principles of Surgery, 10e; 2014 Available at:

http://accesssurgery.mhmedical.com/content.aspx?sectionid=59610874&bookid=980&jumpsectionID=100401453&Resultclick=2 Accessed: March 28,

2017

Copyright © 2017 McGraw-Hill Education. All rights reserved

A. Fasting1. Sphincter of Oddi contracted

2. Gallbladder filling

B. Response to a meal

1. Sphincter of Oddi relaxed

2. Gallbladder emptying

Pathophysiology

Gallstone Types

Gallstones form as a result of solids settling out of solution

Major organic solutes in bile are bilirubin, bile salts, phospholipids, and cholesterol

Gallstones are classified by their cholesterol content

Cholesterol stones

Western countries: approximately 80% of gallstones

Pigment stones

Black

• Western countries: approximately 15-20%

Brown

• Only a small percentage of stones in Western countries

Cholesterol Stones Pure cholesterol stones are uncommon and account for less than 10% of all

stones Typically occur as single large stones with smooth surfaces

Most other cholesterol stones contain variable amounts of bile pigments and calcium, but are always greater than 70% cholesterol by weight Usually multiple stones of varying sizes

May be hard and faceted, or irregular, mulberry-shaped, and soft

Colors range from whitish yellow and green to black

Less than 10% of cholesterol stones are radiopaque



http://accesssurgery.mhmedical.com/ViewLarge.aspx?figid=100401457&gbosContainerID=0&gbosid=0 Accessed: March 28, 2017


Cholesterol Supersaturation

The common primary event in the formation of cholesterol stones is supersaturation of bile with cholesterol

High bile cholesterol levels and cholesterol gallstones are considered as one disease

Cholesterol is highly nonpolar and insoluble in water and bile

Cholesterol solubility depends on the relative concentration of cholesterol, bile salts, and lecithin (the main phospholipid in bile)

Supersaturation is caused by cholesterol hypersecretionrather than by a reduced secretion of phospholipid or bile salts



http://accesssurgery.mhmedical.com/ViewLarge.aspx?figid=100401457&gbosContainerID=0&gbosid=0 Accessed: March 28, 2017


Pigment Stones

Pigment stones contain less than 20% cholesterol and are

dark because of the presence of calcium bilirubinate

Black stones and brown stones have very little in common

aside from cholesterol content and should be considered

separate entities

https://www.flickr.com/photos/jian-hua_qiao_md/3953725382

Black Pigment Stones

Typically small, brittle, black, and sometimes spiculated

Formed by supersaturation of calcium bilirubinate,

carbonate, and phosphate

Most often secondary to hemolytic disorders such as hereditary

spherocytosis and sickle cell disease, and in those with cirrhosis

Almost always form in the gallbladder

In Asian countries such as Japan, black stones account for a

much higher percentage of gallstones than in the Western

hemisphere

Brown Pigment Stones

Typically less than 1 cm in diameter, brownish-yellow, soft, and often mushy

Can form either in the gallbladder or in the bile ducts

Typically secondary to bacterial infection caused by bile stasis

Precipitated calcium bilirubinate and bacterial cell bodies compose the major part of the stone

Typically found in the biliary tree of Asian populations and are associated with stasis secondary to parasite infection

In Western populations, brown stones occur as primary bile duct stones in patients with biliary strictures or other common bile duct stones that cause stasis and bacterial contamination

Diagnostic Imaging of the Gallbladder

Plain Abdominal X-Ray

X-ray

10-15% of gallstones seen on X-ray

Air in the biliary tree

http://www.slideshare.net/shaffar75/ultrasound-of-the-gallbladder

http://medlibes.com/entry/porcelain-gallbladder

Porcelain gallbladder

Ultrasound

Gold standard for diagnosis of cholelithiasis

~85% sensitive for gallstones

False negative results in only 5% of patients (small stones or

contracted gallbladder)

Typically misses stones in the CBD

Ultrasound of normal gallbladder

http://www.derryimaging.com/body-map/ultrasound/

Ultrasound of gallbladder with gallstones

https://commons.wikimedia.org/wiki/File:Ultrasound_image_of_gallbladder_stone_Gallstone_091937515.jpg

Ultrasound of gallbladder “sludge”

http://www.radiologytutorials.com/main.cgi?tut=/main.cgi&frame=main&tt=1&s=2&t=80

Ultrasound of cholecystitis

http://www.radiologyassistant.nl/en/p43a0746accc5d/gallbladder-wall-thickening.html

Ultrasound vs. CT of Cholecystitis

http://www.radiologyassistant.nl/en/p43a0746accc5d/gallbladder-wall-thickening.html

Radionuclide scan (HIDA)

http://www.slideshare.net/shaffar75/ultrasound-of-the-gallbladder

Magnetic Resonance

Cholangiopancreatography (MRCP)

https://mrimaster.com/anatomy/biliary%20system%20anatomy%20(mrcp)/

Percutaneous transhepatic cholangiography (PTC)

"PTC" by J. Guntau at German Wikipedia - Transferred from de.wikipedia to

Commons.(Original text: Endoskopiebilder.de). Licensed under Public Domain via

Endoscopic retrograde

cholangiopancreatography (ERCP)

https://www.ceessentials.net/article41.html

Natural History of Cholelithiasis

Spectrum of Gallbladder Disease

Spectrum of Gallstone Disease

Asymptomatic cholelithiasis

Biliary colic (chronic cholecystitis or symptomatic cholelithiasis)

Acute cholecystitis Calculous cholecystitis

Acalculous cholecystitis

Mirizzi’s syndrome

Choledocholithiasis

Ascending cholangitis

Gallstone pancreatitis

Gallstone ileus

Biliary dyskinesia

Benign gallbladder tumors

Gallbladder carcinoma

Case #1

53 year old female presented for evaluation after she

underwent an echocardiogram which incidentally identified

a 3-cm gallstone

She denied abdominal pain, nausea, vomiting, diarrhea, or

constipation

RUQ US demonstrated cholelithiasis (a large gallstone

measuring 3 cm) without gallbladder wall thickening,

pericholecystic fluid, or a sonographic Murphy’s sign

Asymptomatic cholelithiasis Approximately 30% of people with cholelithiasis end up having

surgery

Symptoms of gallstone disease generally do not change in severity

Each year, approximately 2% of patients with asymptomatic gallstones develop symptoms

Presence of gallstones in a person with asymptomatic or mildly symptomatic disease is not an indication for cholecystectomy

Reasons to recommend cholecystectomy in asymptomatic cholelithiasis

Large stones (> 2 cm in diameter) – they produce acute cholecystitis more often than small stones

Calcified gallbladder – often associated with carcinoma

Case #2

29 year old female presented complaining of episodic

abdominal pain and abdominal bloating approximately 1

hour after eating

RUQ US demonstrated cholelithiasis with a 1.6 cm gallstone

and diffuse gallbladder wall thickening without

pericholecystic fluid, and a negative sonographic Murphy’s

sign

HIDA demonstrated chronic cholecystitis (non-filling of the

gallbladder at 45 minutes, but eventual filling at 4 hours)

Biliary Colic (Chronic Cholecystitis)

Most common form of symptomatic gallbladder disease

Signs/symptoms

Caused by transient gallstone obstruction of the cystic duct

Right upper quadrant pain, but can be epigastric or left abdominal pain

Diagnosis

RUQ ultrasound

Gallstones can be demonstrated in about 95% of cases, and a positive reading for gallstones is almost never in error

About 2% of patients with gallstone disease have normal ultrasound studies

Biliary Colic (Chronic Cholecystitis) (continued)

Complications

Predisposes to acute cholecystitis, common duct stones, and

adenocarcinoma of the gallbladder

Complications are infrequent

Treatment

Medical

Avoiding fatty foods

Dissolution of stones – ursodiol (Actigall)

Surgical

Cholecystectomy is indicated in most patients with symptoms

Case #3

31 year old male presented complaining of epigastric pain,

nausea, and vomiting

On admission to the emergency department, blood pressure

was 180/107. WBC was 7.4

CT angio chest/abdomen/pelvis demonstrated no evidence of an

aortic dissection and no intraabdominal findings

Discharged home

Presented again 12 hours later with RUQ pain and WBC

was 14.9 with a left shift of 80.4% neutrophils

RUQ ultrasound demonstrated gallbladder wall thickening

of 0.6 cm, cholelithiasis, trace pericholecystic fluid, and a

positive sonographic Murphy’s sign

Acute Cholecystitis

In 80% of cases, acute cholecystitis results from obstruction

of the cystic duct by a gallstone

Pathologic changes in the gallbladder

Gangrene and perforation may occur as early as 3 days after

onset, but most perforations occur during the second week

In cases that resolve spontaneously, acute inflammation has

largely cleared by 4 weeks

About 20% of cases of acute cholecystitis occur in the

absence of cholelithiasis (acalculous cholecystitis)

Most cases occur in patients hospitalized with some other illness

Common in trauma victims and patients receiving TPN

Acute Cholecystitis (continued)

Signs/symptoms

RUQ pain and tenderness

Murphy’s sign

Inspiratory arrest with right subcostal region palpation during inspiration

Nausea and vomiting are present in about half of patients, but the vomiting is rarely severe

Fever (usually 38°C to 38.5°C)

High fever and chills are uncommon and should suggest the possibility of complications or an incorrect diagnosis

Labs

WBC elevated

LFTs should be normal

Imaging

US

HIDA


Complications

Suppurative cholecystitis (empyema)

Gangrene

Emphysematous cholecystitis

Perforation – total incidence about 10%

Localized perforation with pericholecystic abscess

Free perforation with generalized peritonitis

Perforation into an adjacent hollow viscus with

formation of a fistula (cholecystenteric fistula)


Treatment

IV fluids

IV antibiotics

Laparoscopic (open) cholecystectomy

Percutaneous cholecystostomy

Prognosis

Overall death rate of acute cholecystitis is about 5%

Algorithm for Management of Acute Cholecystitis

Adapted from:

RUQ pain,

tenderness,

RUQ US

positive

Non-

operative

management

If US

equivocal,

HIDA

Late

cholecystectomy

Good

operative

risk

Advanced

disease,

toxic

Early

cholecystectomy

(or

cholecystostomy)

No

No

Prompt

improvement

Yes

No

Diagnostic

Yes

Case #4

46 year old female presented complaining of RUQ pain

Labs

WBC count 6.8

Total bilirubin 5.8

Alkaline phosphatase 182

AST 237

ALT 516

RUQ US demonstrated cholelithiasis without gallbladder

wall thickening or pericholecystic fluid, and a slightly dilated

CBD (0.8 cm) without dilated intrahepatic bile ducts

ERCP demonstrated a stone in the distal CBD, which was

removed

Choledocholithiasis

Approximately 15% of patients with cholelithiasis have

stones in the bile ducts

Common duct stones are usually accompanied by others in

the gallbladder, but in 5% of cases, the gallbladder is empty

Two possible origins for common duct stones

Secondary common duct stones

Stones develop within gallbladder and pass through cystic duct into CBD

Cholesterol stones

Primary common duct stones

Stones develop within CBD

Pigment stones

Choledocholithiasis (continued)

Symptoms

RUQ, epigastric or sub-sternal pain with referred pain to the right

scapula

Intermittent chills/fever

Jaundice

Transient darkening of urine

Pruritis

Labs

AST/ALT, Alkaline phosphatase, and bilirubin all elevated

WBC may be elevated or normal


Imaging

X-ray

US

CT

MRCP

ERCP


Complications

Intra-hepatic abscesses

Hepatic failure or secondary biliary cirrhosis

Acute pancreatitis

Erosion of a CBD stone through the ampulla gallstone ileus

Hemorrhage (hemobilia)

Treatment

Antibiotics if cholangitis is suspected

ERCP

Cholecystectomy with cholangiogram

Common bile duct exploration

Natural History of Choledocholithiasis

Gallbladder

stones

100

Cholangitis

3

Biliary

colic

2

Pancreatitis

1

Suppurativ

e

cholangitis

Jaundice

3

Asymptomatic

common duct

stones

6

Common

bile duct

stones

15

Rare

Adapted from:

Case #5

28 year old male presented complaining of severe epigastric abdominal pain, nausea, vomiting, and chills

History of a laparoscopic cholecystectomy 3 weeks prior

Febrile (101.4 °F)

Labs

WBC 10.8

Total bilirubin 7.1


AST 130

ALT 408

CT abdomen/pelvis demonstrated intra- and extra-hepatic biliary ductal dilatation

ERCP demonstrated a stone in the CBD, which was extracted

Ascending cholangitis

Bacterial infection of obstructed biliary ducts

Causes

Choledocholithiasis

Biliary stricture

Neoplasm

Less common:

Chronic pancreatitis, ampullary stenosis, pancreatic pseudocyst, duodenal diverticulum, congenital cyst, and parasitic invasion

Iatrogenic cholangitis may complicate transhepatic or T-tube cholangiography

Higher chance of ascending cholangitis once the duct is colonized with bacteria

Predominant organisms (in decreasing frequency) are E. coli, Klebsiella, Pseudomonas, Enterococci, and Proteus

Ascending cholangitis (continued)

Diagnosis is mostly clinical, although RUQ ultrasound can demonstrate dilated intra- and extra-hepatic ducts

Charcot’s triad – present in only 70% of cases

RUQ pain

Fever

Jaundice

Reynolds’ pentad

Charcot’s triad

Altered mental status

Hypotension

Ascending cholangitis (continued)

Treatment

Antibiotics

ERCP

PTC

Common bile duct exploration

Case #6

46 year old female presented complaining of two days of severe abdominal pain, which started in the epigastrium and became diffuse, associated with nausea and vomiting

Labs WBC 21.2

Total bilirubin 2.3


AST 99

ALT 170

Lipase 8059

RUQ US demonstrated a distended gallbladder with mild wall thickening, small pericholecystic fluid, non-mobile stones, and a mildly dilated CBD (0.9 cm)

MRCP demonstrated acute pancreatitis with extensive peripancreaticinfiltration and acute peripancreatic fluid collections, cholelithiasis, choledocholithiasis, and mild biliary dilatation

Gallstone Pancreatitis

Acute pancreatitis due to biliary obstruction

Diagnosis is mostly clinical (history, physical exam, labs)

RUQ ultrasound demonstrates cholelithiasis

CT can be used to find necrotizing pancreatitis, fluid collections,

or other complications but is not technically required to make the

diagnosis

Treatment is supportive initially

Cholecystectomy with cholangiogram prior to discharge

from the hospital if the pancreatitis is mild or moderate to

avoid a recurrent episode

~30% will recur within 6 weeks if CBD is not cleared prior to

discharge

Gallstone Ileus

A mechanical intestinal obstruction caused by a large

gallstone lodged in the lumen

It occurs more often in women, and the average patient age

is about 70 years

Usually presents with obvious small bowel obstruction

The obstructing gallstone enters the intestine through a

cholecystenteric fistula located in the duodenum, colon, or,

rarely, the stomach or jejunum

Stones that cause gallstone ileus are almost always 2.5 cm or

more in diameter

Gallstone Ileus (continued)

Imaging

Abdominal X-ray may show a radiopaque gallstone

Pneumobilia will be seen in about 40% of cases

http://radiopaedia.org/articles/gallstone-ileus

Gallstone Ileus (continued)

Treatment

Emergency laparotomy and removal of the obstructing stone

through a small proximal enterotomy

Leave gallbladder alone at emergency laparotomy

The death rate from gallstone ileus remains about 20%,

largely because of the poor general condition of elderly

patients at the time of laparotomy

Summary

RUQ pain? Fever?Elevated

WBC?

Elevated

LFTs?Diagnosis? Treatment?

Biliary colicYes

(intermittent)No No No US

Laparoscopic

cholecystectomy

Acute

cholecystitis

Yes

(constant)Yes Yes No

US

HIDA

1) Antibiotics

2) Laparoscopic

cholecystectomy

3) Percutaneous

cholecystostomy

Choledocholithiasis Yes No No Yes MRCP

1)ERCP

2) Laparoscopic

cholecystectomy

Ascending

cholangitisYes Yes Yes Yes

Clinical

US

1) Antibiotics

2) ERCP

3) PTC

4) CBD exploration

Gallstone

pancreatitis

Yes

(Epigastric)Maybe Yes Yes

Clinical

US

CT

1)Supportive

2) Laparoscopic

cholecystectomy

Post-Cholecystectomy Syndrome

A heterogeneous group of disorders affecting patients who continue to complain of symptoms after cholecystectomy

The usual reason for incomplete relief after cholecystectomy is that the preoperative diagnosis of chronic cholecystitis was incorrect

An organic cause for the symptoms is more likely to be discovered in patients with severe episodic pain than in those with other complaints

Abnormal liver function studies, jaundice, and cholangitis are other manifestations that indicate residual biliary disease

Patients with suspicious findings should be studied by ERCP or PTC

Benign Gallbladder Tumors

The differentiation from gallstones is based upon observing

whether a shift in position of the projections follows

changes in posture of the patient, since stones are not fixed

Cancer should be suspected in any polypoid lesion that

exceeds 1 cm in diameter

Polyps

Adenomyomatosis

Adenomas

Gallbladder Carcinoma

An uncommon neoplasm that occurs in elderly patients

Associated with gallstones in 70% of cases

The risk of malignant degeneration correlates with the

length of time gallstones have been present

Prevalence in women compared to men is approximately 2:1

Histology – adenocarcinoma is the most common

Scirrhous (60%)

Papillary (25%)

Mucoid (15%)

Gallbladder Carcinoma (continued)

Early direct invasion of the liver and hilar structures and by metastases to the common duct lymph nodes, liver, and lungs

Carcinoma can be incidentally found after cholecystectomy, where the tumor is confined to the gallbladder

Symptoms

Right upper quadrant pain

Obstruction of the cystic duct by tumor sometimes initiates an attack of acute cholecystitis

Other cases present with obstructive jaundice and, occasionally, cholangitis due to secondary involvement of the common duct

Gallbladder carcinoma – Imaging

Gallbladder Carcinoma:

Complications and Prevention

Complications

Intra-hepatic, pericholecystic or within the gallbladder abscesses

Prevention?

Incidence of gallbladder cancer has decreased in recent years as

the frequency of cholecystectomy has increased

Estimated that one case of gallbladder cancer is prevented for

every 100 cholecystectomies performed

Gallbladder Carcinoma: Surgical Treatment

In the few cases when cancer has not penetrated the muscularis mucosae, cholecystectomy alone should suffice

Small invasive carcinoma discovered by the pathologist

Reoperation to perform a wedge resection of the liver bed plus regional lymphadenectomy

Localized carcinoma

Cholecystectomy along with en bloc wedge resection of an adjacent 3-5 cm of normal liver and dissection of the lymph nodes in the hepatoduodenal ligament

More extensive hepatectomies (e.g., right lobectomy) are not worthwhile

There is little that surgery can offer in cases with hepatic metastases or more distant spread

Gallbladder Carcinoma: Prognosis

Radiotherapy and chemotherapy are not effective

palliative measures

About 85% of patients are dead within a year

after diagnosis

The 10% of patients who survive more than 5

years:

Carcinoma was an incidental finding during

cholecystectomy for symptomatic gallstone disease

An aggressive resection has removed all gross tumor

References

CURRENT Diagnosis & Treatment: Surgery, 14e

Gerard M. Doherty

Schwartz’s Principles of Surgery, 10e

F. Charles Brunicardi, Dana K. Andersen, Timothy R.

Billiar, David L. Dunn, John G. Hunter, Jeffrey B. Matthews,

Raphael E. Pollock

The History of Medicine: The Galling Gallbladder.

http://columbiasurgery.org/news/2015/06/11/history-

medicine-galling-gallbladder

#ILookLikeASurgeon #NYerORCoverChallenge

Documents

The Spectrum of Gallbladder Disease